Gold nanoparticles inhibit steroid-insensitive asthma in mice preserving histone deacetylase 2 and NRF2 pathways

• Main Author: Serra, Magda Fraguas
• Publication Date: 2022
• Other Authors: Santana, Amanda da Costa Cotias, Pimentel, Andreza da Silva, Arantes, Ana Carolina Santos de, Pires, Ana Lucia de Aguiar, Deus, Manuella Lanzetti Daher de, Hickmann, Jandir Miguel, Barreto, Emiliano de Oliveira, Carvalho, Vinicius de Frias, Martins, Patricia Machado Rodrigues e Silva, Cordeiro, Renato Sergio Balao, Martins, Marco Aurélio
• Format: Article
• Language: eng
• Source: Repositório Institucional da UFRGS
• Download full: http://hdl.handle.net/10183/254598
• topic: Nanopartículas de ouro; Asma; Espalhamento de raios-x; Gold nanoparticle; Steroid-insensitive asthma; Lung inflammation; NRF2; HDAC2; Oxidative imbalance

Background: Gold nanoparticles (AuNPs) can inhibit pivotal pathological changes in experimental asthma, but their effect on steroid-insensitive asthma is unclear. The current study assessed the effectiveness of nebulized AuNPs in a murine model of glucocorticoid (GC)-resistant asthma. Methods: A/J mice were sensitized and subjected to intranasal instillations of ovalbumin (OVA) once a week for nine weeks. Two weeks after starting allergen stimulations, mice were subjected to Budesonide or AuNP nebulization 1 h before stimuli. Analyses were carried out 24 h after the last provocation. Results: We found that mice challenged with OVA had airway hyperreactivity, eosinophil, and neutrophil infiltrates in the lung, concomitantly with peribronchiolar fibrosis, mucus production, and pro-inflammatory cytokine generation compared to sham-challenged mice. These changes were inhibited in mice treated with AuNPs, but not Budesonide. In the GCresistant asthmatic mice, oxidative stress was established, marked by a reduction in nuclear factor erythroid 2-related factor 2 (NRF2) levels and catalase activity, accompanied by elevated values of thiobarbituric acid reactive substances (TBARS), phosphoinositide 3-kinases δ (PI3Kδ) expression, as well as a reduction in the nuclear expression of histone deacetylase 2 (HDAC2) in the lung tissue, all of which sensitive to AuNPs but not Budesonide treatment. Conclusion: These findings suggest that AuNPs can improve GC-insensitive asthma by preserving HDAC2 and NRF2.